Genetic Variant NM_001115116.2:c.1568T>G (chr2-70985275-T-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001115116.2(ANKRD53):c.1568T>G(p.Leu523Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000195 in 1,026,926 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0000019 ( 0 hom. )

Consequence

ANKRD53
NM_001115116.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0650

Publications

0 publications found

Variant links:

Genes affected

ANKRD53 (HGNC:25691): (ankyrin repeat domain 53) Involved in mitotic metaphase plate congression; regulation of microtubule cytoskeleton organization; and regulation of mitotic cytokinesis. Located in spindle pole. [provided by Alliance of Genome Resources, Apr 2022]

ANKRD53 links:

ENSG00000258881 (HGNC:):

ENSG00000258881 links:

TEX261 (HGNC:30712): (testis expressed 261) Predicted to enable COPII receptor activity. Predicted to be involved in endoplasmic reticulum to Golgi vesicle-mediated transport. Predicted to act upstream of or within positive regulation of apoptotic process. Predicted to be located in cytoplasm. Predicted to be integral component of membrane. Predicted to be active in COPII-coated ER to Golgi transport vesicle. Predicted to be integral component of Golgi membrane and integral component of endoplasmic reticulum membrane. [provided by Alliance of Genome Resources, Apr 2022]

TEX261 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.1259593).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ANKRD53	NM_001115116.2 link	c.1568T>G	p.Leu523Arg	missense_variant	Exon 6 of 6	ENST00000360589.4	NP_001108588.1	Q8N9V6-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ANKRD53	ENST00000360589.4 link	c.1568T>G	p.Leu523Arg	missense_variant	Exon 6 of 6	2	NM_001115116.2	ENSP00000353796.3		Q8N9V6-1
ENSG00000258881	ENST00000606025.5 link	c.475+3640A>C		intron_variant	Intron 5 of 5	5		ENSP00000475641.1		U3KQ87

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000195

AC:

AN:

1026926

Hom.:

Cov.:

AF XY:

0.00000195

AC XY:

AN XY:

512290

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00

AC:

AN:

23508

American (AMR)

AF:

0.00

AC:

AN:

31438

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

18854

East Asian (EAS)

AF:

0.00

AC:

AN:

26722

South Asian (SAS)

AF:

0.00

AC:

AN:

71656

European-Finnish (FIN)

AF:

0.00

AC:

AN:

37318

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4224

European-Non Finnish (NFE)

AF:

0.00000259

AC:

AN:

771020

Other (OTH)

AF:

0.00

AC:

AN:

42186

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.00666416), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.325

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.081

BayesDel_noAF

Benign

-0.35

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0047

.;T

Eigen

Benign

-0.89

Eigen_PC

Benign

-0.95

FATHMM_MKL

Benign

0.11

LIST_S2

Benign

0.55

T;T

M_CAP

Benign

0.034

MetaRNN

Benign

0.13

T;T

MetaSVM

Benign

-0.91

MutationAssessor

Benign

2.0

.;M

PhyloP100

-0.065

PrimateAI

Benign

0.33

PROVEAN

Benign

-1.5

N;N

REVEL

Benign

0.12

Sift

Pathogenic

0.0

D;D

Sift4G

Pathogenic

0.0

D;D

Polyphen

0.12

.;B

Vest4

0.18

MutPred

0.18

.;Gain of disorder (P = 0.0364);

MVP

0.70

MPC

0.65

ClinPred

0.26

GERP RS

0.84

Varity_R

0.17

gMVP

0.44

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over